US9371289B2 - Phenoxyethyl dihydro-1H-isoquinoline compounds - Google Patents
Phenoxyethyl dihydro-1H-isoquinoline compounds Download PDFInfo
- Publication number
- US9371289B2 US9371289B2 US14/888,497 US201414888497A US9371289B2 US 9371289 B2 US9371289 B2 US 9371289B2 US 201414888497 A US201414888497 A US 201414888497A US 9371289 B2 US9371289 B2 US 9371289B2
- Authority
- US
- United States
- Prior art keywords
- compound
- pharmaceutically acceptable
- isoquinoline
- acceptable salt
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- DINRMMYGZZHTSQ-UHFFFAOYSA-N 1-(2-phenoxyethyl)-1,2,3,4-tetrahydroisoquinoline Chemical class N1CCC2=CC=CC=C2C1CCOC1=CC=CC=C1 DINRMMYGZZHTSQ-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 83
- 150000003839 salts Chemical class 0.000 claims abstract description 37
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- YPWZAMDZNBPGFN-UQBPGWFLSA-N 4-[(1s)-1-[[(3r)-2-(2-phenoxyethyl)-3,4-dihydro-1h-isoquinoline-3-carbonyl]amino]ethyl]benzoic acid Chemical compound C([C@@H]1C(=O)N[C@@H](C)C=2C=CC(=CC=2)C(O)=O)C2=CC=CC=C2CN1CCOC1=CC=CC=C1 YPWZAMDZNBPGFN-UQBPGWFLSA-N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- QEGVLHIPOFXEGZ-AVRWGWEMSA-N 4-[(1s)-1-[[(3r)-2-[2-(4-fluorophenoxy)ethyl]-3,4-dihydro-1h-isoquinoline-3-carbonyl]amino]ethyl]benzoic acid Chemical compound C([C@@H]1C(=O)N[C@@H](C)C=2C=CC(=CC=2)C(O)=O)C2=CC=CC=C2CN1CCOC1=CC=C(F)C=C1 QEGVLHIPOFXEGZ-AVRWGWEMSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 32
- YZDXFUGIDTUCDA-UHFFFAOYSA-N isoquinoline-1-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=NC=CC2=C1 YZDXFUGIDTUCDA-UHFFFAOYSA-N 0.000 description 25
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- 210000004027 cell Anatomy 0.000 description 19
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
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- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 15
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- ZGSCZTCQNXFWPS-UHFFFAOYSA-N 1-(2-phenoxyethyl)isoquinoline Chemical compound C(Cc1nccc2ccccc12)Oc1ccccc1 ZGSCZTCQNXFWPS-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
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- 102100024447 Prostaglandin E2 receptor EP3 subtype Human genes 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
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- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
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- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
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- 150000003840 hydrochlorides Chemical class 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
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- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- DXLFSSQSGGCNKP-FQRUVTKNSA-N C[C@H](CC(=O)[C@H]1CC2=C(C=CC=C2)CN1CCOC1=CC=CC=C1)C1=CC=C(C(=O)O)C=C1 Chemical compound C[C@H](CC(=O)[C@H]1CC2=C(C=CC=C2)CN1CCOC1=CC=CC=C1)C1=CC=C(C(=O)O)C=C1 DXLFSSQSGGCNKP-FQRUVTKNSA-N 0.000 description 3
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- DNLDTAMVFGDUPV-HRAATJIYSA-N tert-butyl (3R)-3-[[(1S)-1-(4-methoxycarbonylphenyl)ethyl]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound COC(=O)C1=CC=C(C=C1)[C@H](C)NC(=O)[C@@H]1N(CC2=CC=CC=C2C1)C(=O)OC(C)(C)C DNLDTAMVFGDUPV-HRAATJIYSA-N 0.000 description 3
- BWKMGYQJPOAASG-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CNC(C(=O)O)CC2=C1 BWKMGYQJPOAASG-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
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| US201361824436P | 2013-05-17 | 2013-05-17 | |
| PCT/US2014/037416 WO2014186218A1 (en) | 2013-05-17 | 2014-05-09 | Phenoxyethyl dihydro-1h-isoquinoline compounds |
| US14/888,497 US9371289B2 (en) | 2013-05-17 | 2014-05-09 | Phenoxyethyl dihydro-1H-isoquinoline compounds |
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| US20160052889A1 US20160052889A1 (en) | 2016-02-25 |
| US9371289B2 true US9371289B2 (en) | 2016-06-21 |
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| EP (1) | EP2997015B1 (pt) |
| JP (1) | JP6148400B2 (pt) |
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| CN (1) | CN105209438B (pt) |
| BR (1) | BR112015026967B1 (pt) |
| CA (1) | CA2908400C (pt) |
| EA (1) | EA027306B1 (pt) |
| ES (1) | ES2626976T3 (pt) |
| HU (1) | HUE033574T2 (pt) |
| MX (1) | MX2015015841A (pt) |
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| TW (1) | TWI636046B (pt) |
| WO (1) | WO2014186218A1 (pt) |
| ZA (1) | ZA201507566B (pt) |
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| LT3083562T (lt) * | 2013-12-17 | 2018-01-10 | Eli Lilly & Company | Fenoksietilo cikliniai amino dariniai ir jų aktyvumas kaip ep4 receptoriaus moduliatorių |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| WO2018210992A1 (en) | 2017-05-18 | 2018-11-22 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives |
| RS62440B1 (sr) | 2017-05-18 | 2021-11-30 | Idorsia Pharmaceuticals Ltd | Derivati fenila kao modulatori receptora pge2 |
| RS62398B1 (sr) | 2017-05-18 | 2021-10-29 | Idorsia Pharmaceuticals Ltd | Derivati pirimidina kao modulatori receptora pge2 |
| ES2929309T3 (es) | 2017-05-18 | 2022-11-28 | Idorsia Pharmaceuticals Ltd | Derivados de benzofurano y benzotiofeno como moduladores del receptor PGE2 |
| AU2018269667B2 (en) | 2017-05-18 | 2022-02-03 | Idorsia Pharmaceuticals Ltd | N-substituted indole derivatives |
| WO2022102731A1 (ja) | 2020-11-13 | 2022-05-19 | 小野薬品工業株式会社 | Ｅｐ４拮抗薬と免疫チェックポイント阻害物質との併用によるがん治療 |
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-
2014
- 2014-05-02 TW TW103115871A patent/TWI636046B/zh active
- 2014-05-09 US US14/888,497 patent/US9371289B2/en active Active
- 2014-05-09 EA EA201591915A patent/EA027306B1/ru not_active IP Right Cessation
- 2014-05-09 JP JP2016513099A patent/JP6148400B2/ja active Active
- 2014-05-09 CA CA2908400A patent/CA2908400C/en active Active
- 2014-05-09 WO PCT/US2014/037416 patent/WO2014186218A1/en active Application Filing
- 2014-05-09 KR KR1020157032468A patent/KR101798315B1/ko active IP Right Grant
- 2014-05-09 BR BR112015026967-2A patent/BR112015026967B1/pt active IP Right Grant
- 2014-05-09 PL PL14727692T patent/PL2997015T3/pl unknown
- 2014-05-09 ES ES14727692.7T patent/ES2626976T3/es active Active
- 2014-05-09 EP EP14727692.7A patent/EP2997015B1/en active Active
- 2014-05-09 HU HUE14727692A patent/HUE033574T2/hu unknown
- 2014-05-09 PT PT147276927T patent/PT2997015T/pt unknown
- 2014-05-09 CN CN201480028163.9A patent/CN105209438B/zh active Active
- 2014-05-09 MX MX2015015841A patent/MX2015015841A/es active IP Right Grant
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2015
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- 2015-10-22 SA SA515370035A patent/SA515370035B1/ar unknown
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| WO2013004291A1 (en) | 2011-07-04 | 2013-01-10 | Rottapharm S.P.A. | Cyclic amine derivatives as ep4 receptor agonists |
| WO2013004290A1 (en) | 2011-07-04 | 2013-01-10 | Rottapharm S.P.A. | Cyclic amine derivatives as ep4 receptor antagonists |
| US8642768B2 (en) | 2012-06-29 | 2014-02-04 | Eli Lilly And Company | Dimethyl-benzoic acid compounds |
| US8962659B2 (en) | 2012-06-29 | 2015-02-24 | Eli Lilly And Company | Phenoxyethyl piperidine compounds |
| US20150126555A1 (en) | 2012-06-29 | 2015-05-07 | Eli Lilly And Company | Phenoxyethyl piperidine compounds |
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|---|---|
| HUE033574T2 (hu) | 2017-12-28 |
| TWI636046B (zh) | 2018-09-21 |
| SA515370035B1 (ar) | 2018-01-04 |
| PT2997015T (pt) | 2017-04-24 |
| BR112015026967A2 (pt) | 2017-07-25 |
| EA201591915A1 (ru) | 2016-04-29 |
| CA2908400C (en) | 2017-04-11 |
| AU2014265762A1 (en) | 2015-10-15 |
| US20160052889A1 (en) | 2016-02-25 |
| ZA201507566B (en) | 2017-06-28 |
| JP6148400B2 (ja) | 2017-06-14 |
| CA2908400A1 (en) | 2014-11-20 |
| ES2626976T3 (es) | 2017-07-26 |
| TW201534588A (zh) | 2015-09-16 |
| CN105209438B (zh) | 2017-04-12 |
| JP2016519140A (ja) | 2016-06-30 |
| EP2997015A1 (en) | 2016-03-23 |
| MX2015015841A (es) | 2016-03-04 |
| BR112015026967A8 (pt) | 2018-01-30 |
| WO2014186218A1 (en) | 2014-11-20 |
| KR20150140831A (ko) | 2015-12-16 |
| CN105209438A (zh) | 2015-12-30 |
| BR112015026967B1 (pt) | 2023-01-10 |
| KR101798315B1 (ko) | 2017-11-15 |
| PL2997015T3 (pl) | 2017-09-29 |
| EA027306B1 (ru) | 2017-07-31 |
| EP2997015B1 (en) | 2017-04-05 |
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